To establish a pharmacological experimental platform for the study of cardiac hypoxia using the microelectrode array.

Abstract:

INTRODUCTION:Simultaneous recording of electrical potentials from multiple cells may be useful for physiological and pharmacological research. The present study aimed to establish an in vitro cardiac hypoxia experimental platform on the microelectrode array (MEA). METHODS:Embryonic rat cardiac myocytes were cultured on the MEAs. Following >or=90 min of hypoxia, changes in lactate production (mM), pH, beat frequency (beats per min, bpm), extracellular action potential (exAP) amplitude, and propagation velocity between the normoxic and hypoxic cells were compared. RESULTS:Under hypoxia, the beat frequency of cells increased and peaked at around 42.5 min (08.1+/-3.2 bpm). The exAP amplitude reduced as soon as the cells were exposed to the hypoxic medium, and this reduction increased significantly after approximately 20 min of hypoxia. The propagation velocity of the hypoxic cells was significantly lower than that of the control throughout the entire 90+ min of hypoxia. The rate of depolarisation and Na(+) signal gradually reduced over time, and these changes had a direct effect on the exAP duration. DISCUSSION:The extracellular electrophysiological measurements allow a partial reconstruction of the signal shape and time course of the underlying hypoxia-associated physiological changes. The present study showed that the cardiac myocyte-integrated MEA may be used as an experimental platform for the pharmacological studies of cardiovascular diseases in the future.

authors

Yeung CK,Sommerhage F,Wrobel G,Law JK,Offenhäusser A,Rudd JA,Ingebrandt S,Chan M

doi

10.1016/j.vascn.2009.02.005

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

146-52

issue

3

eissn

1056-8719

issn

1873-488X

pii

S1056-8719(09)00020-3

journal_volume

59

pub_type

杂志文章
  • Sensitivity and specificity of isolated perfused guinea pig heart to test for drug-induced lengthening of QTc.

    abstract:INTRODUCTION:The purpose of this study was to determine the sensitivity and specificity for predicting the liability of a compound to lengthen QTc using isolated, perfused guinea pig hearts (Langendorff preparation). METHODS:QTc (Fridericia correction) was calculated from bipolar transventricular electrograms. Hearts ...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2003.08.003

    authors: Hamlin RL,Cruze CA,Mittelstadt SW,Kijtawornrat A,Keene BW,Roche BM,Nakayama T,Nakayama H,Hamlin DM,Arnold T

    更新日期:2004-01-01 00:00:00

  • HPLC determination of inorganic cation levels in CSF and plasma of conscious rabbits.

    abstract::An HPLC method is described using conductimetric detection for the quantitative determination of sodium, potassium, magnesium, and calcium in cerebrospinal fluid (CSF) and plasma of conscious rabbits. This method enabled the four cations to be estimated with rapidity, sensitivity, accuracy, and precision. The mean mil...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/1056-8719(93)90057-l

    authors: Frosini M,Gorelli B,Matteini M,Palmi M,Valoti M,Sgaragli GP

    更新日期:1993-04-01 00:00:00

  • Rapid HPLC assay with coulometric detection for norepinephrine and 3-methoxy-4-hydroxyphenylglycol in the mouse brain.

    abstract::For the rapid assay of norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) in the mouse brain, we developed a simple method using isocratic HPLC with coulometric detection. This method permits NE and MHPG assay within 5 min in one chromatographic run. Within-run coefficients of variati...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/1056-8719(94)90060-4

    authors: Murai S,Saito H,Masuda Y,Ohkubo N,Itoh T

    更新日期:1994-10-01 00:00:00

  • Optimization and validation of small quantity RNA profiling for identifying TNF responses in cultured human vascular endothelial cells.

    abstract:INTRODUCTION:Affymetrix oligonucleotide microarrays are widely used in basic and applied research (Lander, E.S., (1999). Array of hope. Nature Genetics 21, 3-4; Lockhart, D.J. & Winzeler, E.A. (2000) Genomics, gene expression and DNA arrays. Nature 405, 827-836.) The need for a significant amount of starting RNA has li...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2005.02.004

    authors: Shou J,Qian HR,Lin X,Stewart T,Onyia JE,Gelbert LM

    更新日期:2006-03-01 00:00:00

  • Determination of dopamine concentrations in brain extracellular fluid using microdialysis with short sampling intervals, analyzed by ultra high performance liquid chromatography tandem mass spectrometry.

    abstract:INTRODUCTION:An increase in striatal dopamine is considered essential for the rewarding and reinforcing effects of drugs of abuse. We have developed and validated an ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the analysis of dopamine in rat brain extracellular fluid (...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2015.06.002

    authors: Gottås A,Ripel Å,Boix F,Vindenes V,Mørland J,Øiestad EL

    更新日期:2015-07-01 00:00:00

  • Analysis of spontaneous hippocampal activity allows sensitive detection of acetylcholine-mediated effects.

    abstract:INTRODUCTION:Excitation of Acetylcholine-mediated (Ach) transmission (especially if irreversible) may pose life-threatening adverse events by increasing neuronal network activity. Unfortunately, adequate detection of this liability during early drug development is hampered, because published ex vivo electrophysiologica...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2014.12.001

    authors: Hermann D,van Amsterdam C

    更新日期:2015-01-01 00:00:00

  • A novel approach for the determination of contractile and calcium responses of the basilar artery employing real-time confocal laser microscopy.

    abstract:INTRODUCTION:Intracellular calcium concentration ([Ca(2+)](i)) modifications in endothelial and smooth muscle cells represent a key element in the pathogenesis of cerebral artery vasospasm. Therefore, the present study documented potential application of confocal laser microscopy in the determination of contractile and...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2007.03.002

    authors: Hashimoto T,Ohata H,Nobe K,Sakai Y,Honda K

    更新日期:2007-07-01 00:00:00

  • Cholemic transgenic mice: a novel animal model to investigate the effects of bile acids.

    abstract:INTRODUCTION:Laboratory investigations into cholestatic liver disease and the effects of cholemia on organ function are long-standing subjects of scientific enquiry. A widely-used strategy to investigate these topics relies on animal-based research using experimental animal models. Targeted inactivation of the spgp gen...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2004.06.002

    authors: Ljubuncic P,Yousef I,Bomzon A

    更新日期:2004-11-01 00:00:00

  • Progress in computational toxicology.

    abstract:INTRODUCTION:Computational methods have been widely applied to toxicology across pharmaceutical, consumer product and environmental fields over the past decade. Progress in computational toxicology is now reviewed. METHODS:A literature review was performed on computational models for hepatotoxicity (e.g. for drug-indu...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章,评审

    doi:10.1016/j.vascn.2013.12.003

    authors: Ekins S

    更新日期:2014-03-01 00:00:00

  • CiPA challenges and opportunities from a non-clinical, clinical and regulatory perspectives. An overview of the safety pharmacology scientific discussion.

    abstract::The Safety Pharmacology Society organized a scientific session at its annual conference in 2017 to discuss the challenges and opportunities of the Comprehensive In-Vitro Proarrhythmia Assay (CiPA) paradigm. Our intention was to raise awareness of this initiative with its members and also to gauge the extent to which s...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章,评审

    doi:10.1016/j.vascn.2018.06.005

    authors: Wallis R,Benson C,Darpo B,Gintant G,Kanda Y,Prasad K,Strauss DG,Valentin JP

    更新日期:2018-01-01 00:00:00

  • Continuous monitoring of mitochondrial membrane potential in hepatocyte cell suspensions.

    abstract::We report a simple fluorometric method for the continuous monitoring of mitochondrial membrane potential and cell viability in suspensions of hepatocytes exposed in vitro to cytotoxic agents. Suspensions of freshly isolated hepatocytes (10(6) cells/mL) preloaded with rhodamine 123 (Rh 123, 100 mumol/L) are transferred...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/1056-8719(95)00131-x

    authors: Palmeira CM,Moreno AJ,Madeira VM,Wallace KB

    更新日期:1996-02-01 00:00:00

  • Hybridization buffer systems impact the quality of filter array data.

    abstract:INTRODUCTION:cDNA microarray technology has greatly facilitated mechanistic studies in pharmacology and toxicology. A clean hybridization with minimal background is critical for successful microarray analysis and is highly desired. However, clean hybridization alone is not enough; verification is needed. METHODS:Total...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2004.02.001

    authors: Liu J,Walker N,Waalkes MP

    更新日期:2004-07-01 00:00:00

  • Reprint of "EEG: Characteristics of drug-induced seizures in rats, dogs and non-human primates".

    abstract::Seizures are amongst the most frequent neurological issues encountered in pre-clinical safety testing. The objective was to characterize EEG morphologies and premonitory signs in drug-induced seizures in preclinical species. A comparative (inter-species) retrospective analysis for drug-induced seizures recorded by vid...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2019.106611

    authors: Authier S,Arezzo J,Pouliot M,Accardi MV,Boulay E,Troncy E,Dubuc Mageau M,Tan W,Sanfacon A,Mignault Goulet S,Paquette D

    更新日期:2019-01-01 00:00:00

  • Comparison of different pharmacodynamic models for PK-PD modeling of verapamil in renovascular hypertension.

    abstract:INTRODUCTION:The aim of this work was to compare the suitability of different pharmacodynamic models for PK-PD modeling of verapamil cardiovascular effects in aortic coarctated rats (ACo), a model of renovascular hypertension. METHODS:A "shunt" microdialysis probe was inserted in a carotid artery of anaesthetized sham...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2008.03.002

    authors: Bertera FM,Mayer MA,Opezzo JA,Taira CA,Höcht C

    更新日期:2008-05-01 00:00:00

  • EEG in non-clinical drug safety assessments: Current and emerging considerations.

    abstract::Electroencephalogram (EEG) data in nonclinical species can play a critical role in the successful evaluation of a compound during drug development, particularly in the evaluation of seizure potential and for monitoring changes in sleep. Yet, while non-invasive electrocardiogram (ECG) monitoring is commonly included in...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章,评审

    doi:10.1016/j.vascn.2016.03.002

    authors: Authier S,Delatte MS,Kallman MJ,Stevens J,Markgraf C

    更新日期:2016-09-01 00:00:00

  • Validation of a voltage-sensitive dye (di-4-ANEPPS)-based method for assessing drug-induced delayed repolarisation in beagle dog left ventricular midmyocardial myocytes.

    abstract:INTRODUCTION:Evaluation of drug candidates in in-vitro assays of action potential duration (APD) is one component of preclinical safety assessment. Current assays are limited by technically-demanding, time-consuming electrophysiological methods. This study aimed to assess whether a voltage-sensitive dye-based assay cou...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2009.03.005

    authors: Hardy ME,Pollard CE,Small BG,Bridgland-Taylor M,Woods AJ,Valentin JP,Abi-Gerges N

    更新日期:2009-07-01 00:00:00

  • A novel sulfur mustard (HD) vapor inhalation exposure system for accurate inhaled dose delivery.

    abstract:INTRODUCTION:A custom designed HD exposure system was used to deliver controlled inhaled doses to an animal model through an endotracheal tube. METHODS:Target HD vapor challenges were generated by a temperature controlled bubbler/aerosol trap, while concentration was monitored near real-time by gas chromatography. Ani...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2014.09.009

    authors: Perry MR,Benson EM,Kohne JW,Plahovinsak JL,Babin MC,Platoff GE Jr,Yeung DT

    更新日期:2015-01-01 00:00:00

  • Monophasic action potential in anaesthetized guinea pigs as a biomarker for prediction of liability for drug-induced delayed ventricular repolarization.

    abstract:INTRODUCTION:Drug-induced QT interval prolongation has been one of the critical issues for developing new chemical entities and pharmaceutical companies need to evaluate the risk early in the development stage. At such stage, guinea pigs are appropriate due to their small size requiring only small amounts of test drugs...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2006.11.002

    authors: Tabo M,Kimura K,Ito S

    更新日期:2007-05-01 00:00:00

  • An integrated system for video and telemetric electroencephalographic recording to measure behavioural and physiological parameters.

    abstract:INTRODUCTION:The combined evaluation of physiology and behaviour allows a complete and more comprehensive pre-clinical assessment of central nervous system (CNS) function. An integrated video-telemetric electroencephalography (Video-tEEG) system, which allows the simultaneous and continuous recording of EEG and video i...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2010.04.004

    authors: Moscardo E,Rostello C

    更新日期:2010-07-01 00:00:00

  • Possible use of excretion of tubular epithelial cells for the study of the nephrotoxic effect of xenobiotics.

    abstract::The method of determination of the minute excretion of tubular epithelial cells renders it possible to investigate the course of the nephrotoxic effect of the toxin by the influence of which excretion of tubular round epithelial cells is increased. The nephrotoxic effect of repeated administration of amphotericin B (1...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/s1056-8719(96)00126-8

    authors: Stĕtinová V,Trejtnar F,Kopecký J,Grossmann V,Kvètina J,Kopecká L,Semecký V

    更新日期:1996-12-01 00:00:00

  • The shifting landscape of safety pharmacology in 2015.

    abstract::The relative importance of the discipline of safety pharmacology (which integrates physiology, pharmacologyand toxicology) has evolved since the incorporation of the Safety Pharmacology Society (SPS) as an entity on August 10, 2000. Safety pharmacology (SP), as a synthesis of these other fields of knowledge, is concer...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 社论

    doi:10.1016/j.vascn.2015.05.013

    authors: Pugsley MK,Authier S,Stonerook M,Curtis MJ

    更新日期:2015-09-01 00:00:00

  • Integration of mechanical conditioning into a high throughput contractility assay for cardiac safety assessment.

    abstract:INDUCTION:Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models re...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2020.106892

    authors: Goßmann M,Linder P,Thomas U,Juhasz K,Lemme M,George M,Fertig N,Dragicevic E,Stoelzle-Feix S

    更新日期:2020-09-01 00:00:00

  • The method of long-term catheterization of the vena jugularis in pigs.

    abstract:INTRODUCTION:The pig is one of the most valuable in vivo models in biomedical research, however with only a few well-accessible veins suitable for venipuncture. Moreover, most of the known methods of blood collection are suitable only for a limited time period. The aim of the study was to verify an improved method of l...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2019.106584

    authors: Klein P,Nalos L,Dejmek J,Soukup M

    更新日期:2019-01-01 00:00:00

  • The PEG-switch assay: a fast semi-quantitative method to determine protein reversible cysteine oxidation.

    abstract:INTRODUCTION:Reversible protein cysteine oxidation is recognised as a pivotal post-transitional modification that transduces physiological as well as pathological signalling. Pharmacological interventions that target specific sources of oxidant formation are currently being trialled to ascertain their potential ability...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2013.07.001

    authors: Burgoyne JR,Oviosu O,Eaton P

    更新日期:2013-11-01 00:00:00

  • Rat tail skin temperature monitored noninvasively by radiotelemetry: characterization by examination of vasomotor responses to thermomodulatory agents.

    abstract:INTRODUCTION:Measurement of tail skin temperature (T(sk)) of the rat can provide important information on mechanisms pertaining to physiology, pharmacology, and toxicology. T(sk) is largely under control of peripheral vascular tone, which is also sensitive to most experimental manipulations such as handling and restrai...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/s1056-8719(02)00219-8

    authors: Gordon CJ,Puckett E,Padnos B

    更新日期:2002-03-01 00:00:00

  • Assessment of hepatobiliary function in vivo and ex vivo in the rat.

    abstract::Many xenobiotics cause hepatobiliary toxicity and cholestasis in the rat. Initial assessment of hepatobiliary damage in rats can be accomplished by measuring serum concentrations of bile acids and bilirubin, serum activities of liver-associated enzymes such as 5'-nucleotidase, alkaline phosphatase, gamma-glutamyltrans...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章,评审

    doi:10.1016/1056-8719(94)90024-8

    authors: Handler JA,Kossor DC,Goldstein RS

    更新日期:1994-02-01 00:00:00

  • Insights into toxicology, safety pharmacology, and drug dependence testing: The performance and predictive values of nonclinical tests.

    abstract::The pre-marketing testing of drugs and chemicals is now a paradigm of contribution to the safeguard of public health. As pointed out by the ICH concept paper E14/S7B, there is a need for science-based frameworks that allow a better design, conduction, and interpretation of nonclinical and toxicity tests, particularly,...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2020.106684

    authors: Suarez-Torres JD,Ciangherotti CE,Jimenez-Orozco FA

    更新日期:2020-01-01 00:00:00

  • ADVAN-style analytical solutions for common pharmacokinetic models.

    abstract:INTRODUCTION:The analytical solutions to compartmental pharmacokinetic models are well known, but have not been presented in a form that easily allows for complex dosing regimen and changes in covariate/parameter values that may occur at discrete times within and/or between dosing intervals. METHODS:Laplace transforms...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2015.03.004

    authors: Abuhelwa AY,Foster DJ,Upton RN

    更新日期:2015-05-01 00:00:00

  • A framework to assess the translation of safety pharmacology data to humans.

    abstract::This article outlines a strategy for collecting accurate data for the determination of the sensitivity, specificity and predictive value of safety pharmacology models. This entails performing a retrospective analysis on commonly used safety pharmacology endpoints and an objective assessment of new non-clinical models....

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/j.vascn.2009.05.011

    authors: Valentin JP,Bialecki R,Ewart L,Hammond T,Leishmann D,Lindgren S,Martinez V,Pollard C,Redfern W,Wallis R

    更新日期:2009-09-01 00:00:00

  • A quantitative electroencephalographic method for xenobiotic screening in the canine model.

    abstract::A method, using quantitative electroencephalography (qEEG), was developed for screening xenobiotics in conjunction with neurological examinations, for defining toxicodynamic profiles of certain drugs and chemicals in the dog. The standard 10-channel montage was used to evaluate normotonic, auditory, visual, and somato...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章

    doi:10.1016/1056-8719(94)90008-6

    authors: Jones RD,Greufe NP

    更新日期:1994-08-01 00:00:00